Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.     

Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1

We report a genome-wide association study for open-angle glaucoma (OAG) blindness using a discovery cohort of 590 individuals with severe visual field loss (cases) and 3,956 controls. We identified associated loci at TMCO1 (rs4656461[G] odds ratio (OR) = 1.68, P = 6.1 × 10(-10)) and CDKN2B-AS1 (rs4977756[A] OR = 1.50, P = 4.7 × 10(-9)). We replicated these associations in an independent cohort of cases with advanced OAG (rs4656461 P = 0.010; rs4977756 P = 0.042) and two additional cohorts of less severe OAG (rs4656461 combined discovery and replication P = 6.00 × 10(-14), OR = 1.51, 95% CI 1.35-1.68; rs4977756 combined P = 1.35 × 10(-14), OR = 1.39, 95% CI 1.28-1.51). We show retinal expression of genes at both loci in human ocular tissues. We also show that CDKN2A and CDKN2B are upregulated in the retina of a rat model of glaucoma.     

理论免疫学历史导论

古代的人们已经知道了天花的免疫现象,甚至进行着危险的免疫操作。约1800年琴纳成功地发展了种痘技术。然而,琴纳的发现在将近100年的长时间内对了解和治疗其他疾病并未发生影响。这正如埃尔利希指出的:“琴纳的发现所以是孤立的,原因是关于传染病的原因和本质的理论概念未发展的缘故。”     

DNA重组体技术在作物改良中的应用

引言近几十年来,DNA技术已获得重大进展。尽管遗传工程仍处在发展阶段,但它必将成为控制植物特性的一种强有力的工具,诸如除草剂与杂草的竞争性、光合效率、营养增强能力、应激忍耐力、固N能力和次生植物再生的生产。传统的常规遗传控制手段是进行品种改良的育种方法。植物的育种,就是从具不良性状的亲本杂交后代中选择优良性状,也许同时存在一个或两个以上的性状是不需要的。植物育种的一个典型的步骤,通常是通过选择优     

在鹰嘴豆的果实组织中光合~(14)CO_2固定产物与有关酶的活性

尽管许多豆科植物,包括鹰嘴豆的果实组织进行光合CO_2的同化是众所周知的,但是,对于在这些组织中CO_2固定的途径,特别是对磷酸烯醇式丙酮酸羧化酶(EC4、1、1、31)的作用还不够清楚。我们己从鹰嘴豆(Cicer arictinum L)的荚果壳、种皮(果实组织)及其苞叶中测定到一些卡尔文循珠和C_4代谢的主要酶的活性,光照和黑暗中~(14)CO_2固定速率和光合CO_2固定的最初产物。对1,5——二磷酸核酮糖羧化酶(EC4、1、1、39)和其它卡尔文循环的酶,即NADP~+——甘油醛—3—磷酸脱氢酶(EC1、2、1、13),NAD~+——甘油醛—3—磷酸脱氢酶(EC1、2、1、12)和5——磷酸核酮糖激酶(EC2、7、1、19)的活性和磷酸烯醇式丙酮羧化酶以及其他C_4代谢的酶,也就是说,对NADP~+—苹果酸脱氢酶(EC_1、1、1、82)、NAD~+—苹果酸脱氢酶(EC1、1、1、37)NADP~+—苹果酸酶(EC1、1、1、40)、NAD~+—苹果酸酶(EC1、1、1、39)、谷氨酸草酰乙酸转氨酶(EC2、6、1、2)和谷氨酸丙酮酸转氨酶(EC2、6、1、2)的活性进行了比较。一般说来,磷酸烯醇式丙酮酸羧化酶和其他C_4代谢的酶,在荚果壳和种皮中的含量比在叶片中的含量为高。荚果壳和种皮在光照和黑暗中~(14)CO_2固定的速率高于叶子。说明在果实组织短期的~(140CO_2同化,象主要标记产物一样产生苹果酸,标记的3—磷酸甘油酸却较少,而在叶片中主要产物合成为3—磷酸甘油酸。显然,鹰嘴豆在果实组织中是利用磷酸烯醇式丙酮酸羧化酶再固定呼吸放出的CO_2。     

Evolution of the genetic code, protein synthesis and nucleic acid replication

A better definition of the structural and thermodynamic determinants of the interaction of nucleic acids with proteins is shedding light on the origin of the genetic code, protein synthesis, and nucleic acid replication. This is also allowing to show a consistent biochemical framework for the appearance of these fundamental synthetic mechanisms. This article reviews recent significant developments in the field, and discusses an integrated model for a biochemically plausible evolution of these fundamental mechanisms of synthesis. This model is based on sequence-specific interactions between abiotically synthesized polynucleotides and polypeptides, and can account for a coordinate evolution of the genetic code, protein synthesis, and nucleic acid replication in living cells.     

Beyond blood pressure: new roles for angiotensin II

Since the discovery 100 years ago by Tigerstedt and Bergman of renin, an acid protease generating angiotensin peptide, numerous discoveries have advanced our understanding of the renin-angiotensin system (RAS). The recent cloning of angiotensin receptors and the availability of specific receptor ligands have allowed characterization of angiotensin-receptor-mediated actions, and an increasing number of studies using biochemical, pharmacological and molecular biological methods has focused on the many different physiological actions of the RAS in various tissues. Angiotensin II, the main effector peptide of the RAS, exerts most of its known actions in blood pressure control and body fluid homeostasis via the AT, receptor. AT, receptors not only play a role in growth control and cell differentiation but have been implicated in apoptosis and tissue regeneration. This review focuses on the extrarenal functions of angiotensin, especially in neuronal cells and the nervous system, and on recent advances in angiotensin receptor research.